Primary lateral sclerosis (PLS) is the rarest form of sporadic motor neuron disease (MND), affecting only upper motor neurons. Although distinct from ALS in that survival is not an immediate concern, PLS is a relentless disease that causes life-long, progressive and severe motor dysfunction. Due to its extreme rarity, PLS has been largely neglected and seldom investigated systematically in a large number of patients. In fact, PLS cases have never been included in any clinical trials in ALS. In addition, current diagnostic criteria require a waiting period of 3 to 4 years before PLS can be diagnosed, which is extremely frustrating for patients and their physicians. In short, our knowledge base for PLS is largely limited, and systematic research has been scanty to date. To improve upon this reality, we propose to hold a highly scientific, international conference on PLS. Most ALS experts agree that PLS holds a key to understanding the disease mechanisms of MNDs, particularly ALS. The organizing committee, which consists of 3 women and 3 men of diverse ethnic/racial origins, proposes to hold a R13 conference on May 3rd and 4th, 2019, immediately before the AAN annual meeting at the Philadelphia Airport Marriott. More than 35 speakers and moderators will participate, representing 30% women, ethnic/racial minorities, and 11 international investigators. All of these individuals, in one way or another, specialize in PLS and have published related scientific papers. The conference will include discussions on the clinical spectrum of PLS and MNDs that mimic it, cognitive impairment which is prevalent in PLS, electrophysiology including cortical hyperexcitability, neuroimaging changes, genetics that can identify definable diseases among PLS phenotypes, biological biomarkers particularly emerging lipidomics and mitochondrial abnormalities, measuring PLS disease progression including potential new outcome measures, and clinical trials in PLS. The keynote speech by Ian Mackenzie, MD, FRCPC, will be on ?Neuropathological and Biological Views on PLS, ALS, and FTD.? A panel discussion will be devoted to (1) Revising PLS Diagnostic Criteria, for which we aim to establish practical and effective criteria and (2) Establishing an International PLS Registry. The PLS Registry will encourage future international collaborations and broader access to patients with this rare disease, thus enabling rigorous scientific investigations. The conference format is innovative, characterized by brief presentations that will allow time for extensive, general discussion among the attendees. We will invite young investigators who wish to specialize in PLS or at least MND research. The inclusion of women and minorities in particular is especially important as the field lacks Black and Hispanic representation. We will publish at least one paper on newly developed diagnostic criteria. Our proposed conference will incite international collaborations and effective future research in PLS, including successful clinical trials. After this conference, PLS will no longer be considered a neglected disease.